We have tested the feasibility of EBV transformation as a means of creation of human monoclonal antibodies to tetanus toxoid, vericella-zoster virus, and melanoma cell surface antigens. We have created monoclonal antibodies to tetanus toxoid and varicella-zoster virus and characterized these. Antibodies of both IgM and IgG isotypes have been created against melanoma cell surface antigens and have been sustained for months in limit dilution cultures as well. We are testing means to expand the quantities of antibody generated by this technique and the duration of antibody secretion, as well as means to improve selection of B cells for EBV transformation in the melanoma system. Our ultimate aim is to develop an in vitro EBV transformation as a means to production of human monoclonal antibodies that are useful for treatment and diagnosis of human infectious and neoplastic disease. (AB)